Infection continues to contribute to morbidity and mortality late after hematopoietic stem cell transplant (HCT). The development of rational evidence-based guidelines for immunizing patients post HCT could substantially reduce this risk, particularly in view of the severity of many vaccine preventable infections in the naive unimmunized host. The efficacy of post HCT vaccination strategies, including the 2000 CDC guidelines, has not been tested in large numbers of patients. Over the last decade, over 250 recipients of an allogeneic HCT at this institution have been vaccinated, with serum and PBL collected to analyze the development of antigen specific responses. Our preliminary data in recipients of TCD HCT suggests that patient age, donor type, and the use and/or method of T cell depletion (TCD) significantly influence the ability of patients to respond to immunization at fixed times post transplant. We hypothesize that current immunization guidelines may not have adequately factored in the prolonged and variable immunodeficiency observed in unrelated and mis-matched related transplant recipients and that certain in vitro parameters of lymphoid reconstitution can be used effectively as surrogate markers to identify appropriate timing for immunization with killed and live vaccines. The specific aims of this grant are therefore 1) to examine and compare the ability of children and adults following HLA-matched, mis-matched related or unrelated HCT to develop and maintain protective antibody titers following vaccination with tetanus, polio, encapsulated bacteria, Hepatitis B, and measles by evaluating pre and sequential post vaccination titers in previously vaccinated patients who have titers available and/or serum frozen for analysis, 2) to examine, in a large retrospective analysis, whether a limited number of in vitro parameters of lymphoid reconstitution (e.g. CD4 cell count, PHA, through IgG serum level) can be used as surrogate markers to determine appropriate times to initiate post HCT re-vaccination, and 3) based on these data to develop recommendations for the timing and scheduling of re-vaccination post HCT which can be prospectively tested in recipients of T cell depleted or unmodified related and unrelated HCT to increase the proportion of long-term transplant survivors with durable immunity against vaccine-preventable disease.